Liver diseases and low serum albumin as potential confounders in the association between low total cholesterol and elevated all-cause and cancer mortality: The Japan Multi-Institutional Collaborative Cohort (J-MICC) study.
Level 3 - non-randomized controlled study
Prospective multicenter cohort study
PubMed 41484028 · doi:10.1016/j.jacl.2025.11.009
What was done
Researchers analyzed 55,677 participants aged 35 to 69 years from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study who were not taking cholesterol-lowering medications at baseline, followed over 10.1 years. Participants with self-reported cardiovascular disease (CVD) and cancer at baseline were excluded. Cohort-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals for all-cause, CVD, and cancer mortality, comparing participants with total cholesterol <160 mg/dL against those with 160 to <200 mg/dL, with and without exclusion of liver diseases and adjustment for baseline serum albumin.
What was found
Low total cholesterol (<160 mg/dL) was initially significantly associated with elevated all-cause and cancer mortality. After excluding baseline liver diseases and adjusting for serum albumin, the associations were no longer statistically significant: - All-cause mortality: HR 1.37 (95% CI, 0.99–1.87) in men; HR 0.96 (95% CI, 0.46–2.02) in women. - Cancer mortality: HR 1.06 (95% CI, 0.66–1.71) in men; HR 1.39 (95% CI, 0.58–3.34) in women. For CVD mortality, risk remained elevated in men with low total cholesterol, whereas in women it was non-significant regardless of liver disease exclusion and albumin adjustment (exact CVD hazard ratios were not reported in the abstract).
Why it matters
These findings suggest that the apparent association between low total cholesterol and higher non-cardiovascular mortality in observational studies is largely driven by reverse causation or confounding from pre-existing liver disease and poor nutritional status.
Limits
The study is observational and conducted exclusively in Japanese adults. Initial unadjusted effect sizes, exact numbers for CVD mortality hazard ratios, and detailed diagnostic criteria for liver diseases were omitted from the abstract. Residual confounding from unmeasured conditions cannot be excluded.
Cited by
- supports Low cholesterol levels are associated with an increased incidence of cancer.